{"title":"Cluster of differentiation 36-engineered photosynthetic cyanobacteria enable immunometabolic reprogramming in triple-negative breast cancer","authors":"Yuanhang Li, Zhengxin Yu, Ying Yang, Jingyang Wang, Yuhan Wang, Yichuan Ma, Jin Ai, Lanya Li, Jinchao Zhang, Zhenhua Li, Huifang Liu","doi":"10.1016/j.actbio.2026.08.025","DOIUrl":"10.1016/j.actbio.2026.08.025","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) exhibits profound resistance to immunotherapy, largely due to a tumor microenvironment constrained by dysregulated lipid metabolism and persistent hypoxia. Excessive fatty acid uptake mediated by the scavenger receptor CD36 (Cluster of differentiation 36) imposes metabolic stress on immune cells while simultaneously fueling tumor growth, whereas hypoxia independently enforces immune exhaustion and macrophage immunosuppression. Despite extensive efforts, targeting either pathway alone has yielded limited therapeutic benefit, underscoring the need for coordinated immunometabolic intervention. Here, we report a living biohybrid strategy that simultaneously regulates lipid metabolism and oxygen availability to reprogram the TNBC microenvironment. By engineering photosynthetic <em>Synechococcus cyanobacteria</em> with surface-displayed anti-CD36 antibodies, we construct a dual-functional system (Syne@aCD36) capable of blocking CD36-mediated fatty acid uptake while generating oxygen in situ under light stimulation. This coordinated regulation alleviates lipid-induced metabolic stress and hypoxia-driven immune suppression, thereby restoring CD8⁺ T cell cytotoxicity, reversing exhaustion phenotypes, and promoting pro-inflammatory macrophage polarization. In an aggressive 4T1 TNBC model, Syne@aCD36 induces robust tumor growth inhibition, enhances immune infiltration, and exhibits minimal systemic toxicity. This work establishes a previously unexplored paradigm for immunometabolic therapy by integrating metabolic checkpoint blockade with photosynthetic oxygenation, providing a promising strategy for immunometabolic remodeling in lipid-rich and hypoxic tumor microenvironments.</div></div><div><h3>Statement of significance</h3><div>We focus on the fact that excessive fatty acid uptake and tumor hypoxia cooperatively drive immunosuppression and T cell exhaustion in the tumor microenvironment. Our Syne@aCD36 platform possesses two innovations:</div><div>1. A dual-function living therapeutic system.</div><div>Syne@aCD36 blocks CD36-mediated fatty acid uptake on tumor and immune cells while simultaneously generating oxygen through photosynthesis under light stimulation, thereby alleviating lipid metabolic stress and tumor hypoxia in situ.</div><div>2. Synergistic immunometabolic reprogramming.</div><div>By concurrently regulating lipid metabolism and oxygen availability, Syne@aCD36 restores CD8⁺ T cell cytotoxicity, reduces exhaustion phenotypes, and promotes pro-inflammatory macrophage polarization, leading to enhanced immune infiltration and tumor growth suppression.</div><div>Our study provides a strategy for tumor immunotherapy through integrated regulation of metabolic checkpoints and the tumor microenvironment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 437-452"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta BiomaterialiaPub Date : 2026-10-01Epub Date: 2026-08-15DOI: 10.1016/j.actbio.2026.08.024
Zexiang Li, Linpeng Liu, Yan Song, Zhizheng Zhou, Lu Zhou, Xinyu Cai, Liangjv Duan, Yanhong Dong, Jie Zhao, Lingwan Hao, Jingting Wang, Rujian Jiang
{"title":"Quaternary ammonium compound-based ionic liquid with microwave responsiveness for treating deep tissue infections without compromising biocompatibility","authors":"Zexiang Li, Linpeng Liu, Yan Song, Zhizheng Zhou, Lu Zhou, Xinyu Cai, Liangjv Duan, Yanhong Dong, Jie Zhao, Lingwan Hao, Jingting Wang, Rujian Jiang","doi":"10.1016/j.actbio.2026.08.024","DOIUrl":"10.1016/j.actbio.2026.08.024","url":null,"abstract":"<div><div>Quaternary ammonium compounds (QACs) hold great promise as alternatives to conventional antibiotics due to their broad-spectrum antibacterial activity and minimal propensity for inducing bacterial drug resistance. However, their inherent cytotoxicity and pro-inflammatory property perpetuate an intractable efficacy-biocompatibility trade-off, severely limiting clinical translation. Herein, aimed to solve this dilemma, we developed a microwave-responsive ionic liquid (IL) via the integration of QACs with an anti-inflammatory anionic organic compound, enabling synergistic bactericidal efficacy through microwave-induced hyperthermia while concomitantly alleviating QAC-related toxicity and inflammation. After loading into bacteria-targeted hollow polydopamine nanoparticles (HPDA NPs), this IL-based nanoplatform exhibited selective biocidal discrimination between bacterial and mammalian cells, fundamentally mitigating QAC-related cytotoxicity. Notably, embedding these nanoparticles into poly (vinyl pyrrolidone) MNs (IL@HPDA@MN) achieved up to 99.8% bactericidal efficiency coupled with robust anti-inflammatory effects in a mouse subcutaneous abscess model, leading to accelerated abscess resolution and tissue regeneration that outperformed clinical antibiotics. Beyond resolving the QAC-centric efficacy-biocompatibility paradox, this work provides a generalizable framework for engineering toxic cationic antibacterial agents into biocompatible, targeted therapeutics, offering a transformative approach for treating deep-seated bacterial infections that are refractory to traditional therapies.</div></div><div><h3>Statement of significance</h3><div>Quaternary ammonium compounds (QACs) are promising alternatives to conventional antibiotics due to their broad-spectrum activity and low resistance risk. Yet, their clinical adoption remains paralyzed by an inherent trade-off between bactericidal efficacy and unacceptable cytotoxicity, pro-inflammation. Here, we break this deadlock by rationally integrating a QAC with an anti‑inflammatory organic compound to form a microwave-responsive ionic liquid (IL). When encapsulated in bacteria-targeted hollow polydopamine nanoparticles and further loaded into a dissolvable microneedle patch, this IL-based platform achieves potent bacterial killing under mild microwave irradiation while exhibiting negligible toxicity toward mammalian cells. In a murine subcutaneous abscess model, the system rapidly resolves deep-seated infections and curtails local inflammation, achieving therapeutic outcomes that rival or surpass those of clinical antibiotics. Beyond offering a ready-to-use strategy for treating refractory deep-tissue infections, this work establishes a generalizable paradigm for converting toxic cationic antimicrobials into biocompatible, spatially controllable therapeutics.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 421-436"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta BiomaterialiaPub Date : 2026-10-01Epub Date: 2026-09-09DOI: 10.1016/j.actbio.2026.09.001
Matisse A. Laurens, Mahyar Foumani, Amir A. Zadpoor, Mohammad J. Mirzaali
{"title":"Scaffold-guided breast reconstruction: A review of current scaffold architectures, materials and fabrication methods","authors":"Matisse A. Laurens, Mahyar Foumani, Amir A. Zadpoor, Mohammad J. Mirzaali","doi":"10.1016/j.actbio.2026.09.001","DOIUrl":"10.1016/j.actbio.2026.09.001","url":null,"abstract":"<div><div>Breast cancer (BC) remains one of the most prevalent malignancies globally, with mastectomy frequently required as part of treatment. This creates a critical clinical demand for effective breast reconstruction strategies. Conventional reconstruction methods, such as silicone implants, autologous fat grafting, and free-flap surgery, have notable drawbacks. Scaffold-guided breast reconstruction (SGBR) is a promising alternative that relies on biocompatible, biodegradable scaffolds to support and direct the regeneration of vascularized soft tissue. This review summarizes the current state of SGBR approaches, emphasizing scaffold architecture, biomaterials, and fabrication techniques. Various scaffold configurations, including fibrous, porous, hydrogel-based, mesh-like, and composite architectures, are discussed, along with natural and synthetic polymeric biomaterials. The integration of advanced additive manufacturing (AM) technologies is also explored, highlighting their role in enabling patient-specific scaffold designs. The review outlines key biological and mechanical criteria for a successful reconstruction, with particular attention to challenges such as neovascularization and tumor recurrence. Although preclinical studies have yielded promising outcomes, clinical translation remains limited, highlighting the need for continued research to optimize scaffold functionality, integration, and long-term performance.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 1-22"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PFSSTKT(PFS)-functionalized Hierarchical Porous ECM Scaffolds Facilitate Articular Cartilage Regeneration through the Recruitment of Endogenous Stem Cells and Chondrogenic Induction","authors":"Mingxue Chen, Jiang Wu, Hao Wang, Yongkang Yang, Xiang Sui, Liwei Fu, Quanyi Guo","doi":"10.1016/j.actbio.2026.02.026","DOIUrl":"10.1016/j.actbio.2026.02.026","url":null,"abstract":"<div><div>Injury to articular cartilage remains a major clinical challenge owing to its limited self-healing capacity. Current cell-based therapies are limited by issues such as dedifferentiation and regulatory hurdles, whereas existing scaffold systems often lack the essential biochemical signals necessary for effective tissue regeneration. Consequently, biomimetic acellular strategies capable of recruiting endogenous stem cells while establishing a conducive biochemical microenvironment to direct their chondrogenic differentiation are needed. In this study, we developed a bioactive, hierarchical porous extracellular matrix (ECM) scaffold fabricated via low-temperature deposition manufacturing (LDM) and functionalized with the bone marrow-homing peptide PFS (amino acid sequence PFSSTKT) to increase <em>in situ</em> cartilage regeneration. The scaffold preserves the native biochemical characteristics of ECM while enabling stable functionalization with the chemoattractant peptide PFS. In vitro studies demonstrated that the PFS-functionalized ECM scaffold exhibited favorable biocompatibility and supported cell adhesion, migration, and proliferation. In vivo studies using a rabbit full-thickness cartilage defect model further showed enhanced endogenous stem cell recruitment and hyaline-like cartilage regeneration in the PFS-ECM group compared with the ECM and control groups. The regenerated tissue exhibited improved matrix composition, biomechanical properties, and histological scores. Collectively, this work presents a cell-free, biofunctional ECM-based scaffold strategy that promotes endogenous repair of articular cartilage, providing a promising approach for cartilage regeneration without exogenous cell transplantation.</div></div><div><h3>Statement of Significance</h3><div>Articular cartilage repair remains a significant clinical challenge. While current cell-based therapies face limitations such as dedifferentiation, conventional scaffolds often lack essential bioinductive signals. To address this challenge, we have developed a bioactive extracellular matrix scaffold functionalized with the chemotactic peptide PFS. In this design, the PFS peptide enhances endogenous stem cell recruitment, while the ECM provides a chondrogenic microenvironment. Experimental results confirmed that this scaffold significantly promotes stem cell migration and chondrogenic differentiation. Animal studies demonstrated that the PFS-ECM group outperformed control groups in cell recruitment, hyaline cartilage regeneration, and mechanical properties, offering a promising cell-free solution with translational potential for clinical cartilage repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"224 ","pages":"Pages 207-222"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146203583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Supramolecular dynamic hydrogels loaded with bevacizumab nanoparticles promote hyaline cartilage regeneration by inhibiting angiogenesis","authors":"Aikang Li, Zilu Jiao, Peng Liu, Mingxin Lin, Jiayou Chen, Rongji Liang, Jingtao Huang, Yaohang Yue, Fuyang Cao, Hongbo You, Hui Zeng, Kunyu Zhang, Jianjing Lin","doi":"10.1016/j.actbio.2026.04.028","DOIUrl":"10.1016/j.actbio.2026.04.028","url":null,"abstract":"<div><div>After joint cartilage injury, due to abnormal vascular invasion, the repaired tissue often forms fibrous cartilage with poor mechanical properties, not matching normal articular hyaline cartilage. The overexpression of vascular endothelial growth factor (VEGF) is considered a significant cause of hyaline cartilage repair failure, while bevacizumab, a commonly used clinical VEGF inhibitor, exhibits a potent anti-angiogenic effect. Therefore, this study combines bevacizumab-loaded nanoparticles with host-guest macromer dynamic hydrogels (HBN hydrogel) to form a composite system, delivering bevacizumab through sustained release to inhibit angiogenesis, improve the cartilage regeneration microenvironment, and thus promote <em>in situ</em> hyaline cartilage repair. The dynamic structure of the host-guest macromer hydrogel supports cell adhesion, aggregation, and spreading within a three-dimensional network, promoting stem cell chondrogenic differentiation under three-dimensional culture conditions. The HBN hydrogel effectively inhibits vascular ingrowth and promotes hyaline cartilage formation when implanted subcutaneously in nude mice. In the orthotopic rat knee defect model, the HBN hydrogel significantly enhanced the quality of <em>in situ</em> repair by promoting anti-inflammatory M2 macrophage polarization and suppressing catabolic enzymes, thereby regenerating hyaline cartilage that closely mirrors native tissue. Ultimately, by synergistically coupling an adaptive three-dimensional mechanical network with the sustained anti-angiogenic and immunomodulatory release of bevacizumab, this composite system provides a highly translational platform for joint repair.</div></div><div><h3>Statement of significance</h3><div>Cartilage repair remains challenging because regenerating neotissue often turns into fibrocartilage due to abnormal blood vessel invasion. We introduce a dynamic host–guest macromer (HGM) hydrogel loaded with bevacizumab nanoparticles to block vascular invasion and promote true hyaline cartilage regeneration. Unlike traditional static hydrogels, this dynamic system supports cell adhesion and spreading in 3D, providing a more favorable environment for tissue formation. <em>In vivo</em> studies show that the HGM hydrogel induces smooth, cartilage-like tissue with minimal vascularization. This work offers a supramolecular materials-based strategy to regulate angiogenesis and inspire therapeutic approaches for hyaline cartilage repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"224 ","pages":"Pages 223-238"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta BiomaterialiaPub Date : 2026-10-01Epub Date: 2026-09-01DOI: 10.1016/j.actbio.2026.08.057
Qiuyu Wang, Qiwei Chen, Di Li, Xueke Jia, Jie Ren, Hezhen Xie, Fei Hu, Xiaoxue Wang, Xueyang Zhang
{"title":"A ROS-responsive coordination nanoplatform integrates antibacterial activity with STING-targeted immunomodulation to attenuate periodontitis","authors":"Qiuyu Wang, Qiwei Chen, Di Li, Xueke Jia, Jie Ren, Hezhen Xie, Fei Hu, Xiaoxue Wang, Xueyang Zhang","doi":"10.1016/j.actbio.2026.08.057","DOIUrl":"10.1016/j.actbio.2026.08.057","url":null,"abstract":"<div><div>Antibacterial treatment reduces residual bacterial burden in periodontitis, but rapid bacterial killing and lysis can also increase exposure to danger signals such as bacterial DNA (bDNA), which can contribute to cGAS–STING-associated innate immune activation. To address this bactericidal stress-associated inflammation, we constructed a ROS-responsive coordination nanosystem, CPLEA, in which the STING inhibitor C-176 was incorporated during Ag⁺-mediated co-assembly of epicatechin and the sulfur-containing PEG ligand methoxy poly(ethylene glycol)–dihydrolipoic acid (mPEG-DHLA), thereby integrating antibacterial activity with the regulation of post-bactericidal STING-associated inflammation. Without compromising bacterial killing, CPLEA promoted C-176 release under oxidative conditions, and the release profile showed temporal overlap with bacterial killing and bDNA exposure. CPLEA attenuated the inflammatory state of macrophages and relieved the suppression of hPDLSC osteogenic differentiation by macrophage-conditioned medium. Transcriptomic analysis indicated downregulation of cytosolic DNA sensing, NF-κB, IL-17, and osteoclast differentiation programs. In a ligature-induced mouse model of periodontitis, CPLEA attenuated local inflammation and TRAP-positive osteoclast accumulation and reduced alveolar bone loss. Collectively, these findings support bactericidal stress-associated STING signaling as a relevant target during local antibacterial treatment of periodontitis and position CPLEA as a feasible materials-based approach for this purpose.</div></div><div><h3>Statement of significance</h3><div>Periodontitis treatment often requires additional antimicrobial control after mechanical debridement, yet rapid bacterial killing and lysis can increase the exposure of bacteria-derived danger signals and thereby sustain host inflammatory responses. This study develops an oxidation-responsive coordination nanoplatform that integrates antibacterial activity with STING-targeted immunomodulation. By incorporating the STING inhibitor C-176 into an Ag⁺-mediated coordination system, CPLEA enables oxidation-promoted C-176 release within a temporal window overlapping bacterial killing and bacterial DNA exposure. The study further demonstrates that early C-176 intervention more effectively regulates STING-associated inflammatory signaling than delayed intervention. CPLEA attenuated macrophage inflammatory responses, alleviated inflammation-associated suppression of periodontal ligament stem cell osteogenic differentiation, and reduced inflammation, osteoclast accumulation, and alveolar bone loss in experimental periodontitis. These findings highlight the importance of immunomodulator availability during the early phase of bactericidal treatment and provide a biomaterials strategy for integrating residual bacterial control with local host modulation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 541-561"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta BiomaterialiaPub Date : 2026-10-01Epub Date: 2026-09-03DOI: 10.1016/j.actbio.2026.09.002
Julian M. Jimenez, Badri Narayanan Narasimhan, Zihou Ye, Kun-Che Peng, Stephanie I. Fraley
{"title":"Transient calcium signaling reprograms YAP mechanosensitivity through actin remodeling","authors":"Julian M. Jimenez, Badri Narayanan Narasimhan, Zihou Ye, Kun-Che Peng, Stephanie I. Fraley","doi":"10.1016/j.actbio.2026.09.002","DOIUrl":"10.1016/j.actbio.2026.09.002","url":null,"abstract":"<div><div>YAP is a central regulator of cell fate, proliferation, and tissue homeostasis that integrates physical cues from the extracellular matrix (ECM). While stiff environments canonically drive YAP nuclear localization and soft environments promote cytoplasmic sequestration, the logic by which cells integrate mechanical inputs with transient biochemical signals remains poorly defined. Here, we examine how intracellular calcium transients interact with substrate compliance to regulate YAP dynamics and transcriptional outputs across epithelial, myoblast, and fibroblast lineages. Using collagen-coated polyacrylamide hydrogels with tunable mechanics, we show that substrate compliance shapes the kinetics of calcium signaling, calcium-mediated actin remodeling, and YAP nuclear shuttling. We demonstrate that calcium signaling can transiently relax baseline mechanical constraints on YAP activity, triggering nuclear translocation and transcriptional activation even on compliant or non-adhesive substrates where YAP is classically suppressed. We identify substrate compliance as a biophysical regulator that filters the transduction of calcium transients into gene-specific programs. Targets such as CYR61 are induced across all mechanical contexts tested, whereas targets like CTGF and AREG require permissive mechanical conditions. These results suggest a preliminary model in which the mechanical state of the cell tunes the activation barrier for YAP-dependent transcription, enabling context-dependent responses to universal biochemical triggers. We show that destabilizing the F-actin cytoskeleton by promoting depolymerization or sequestering actin monomers results in attenuation of the calcium-mediated YAP activity, while stabilizing F-actin results in amplification of YAP activity in response to calcium stimulation. This work reveals a fundamental mechanism by which transient signals integrate with matrix mechanics to produce distinct YAP-dependent outcomes, suggesting new strategies for controlling cell fate in regenerative medicine and engineered tissues.</div></div><div><h3>Statement of significance</h3><div>Although YAP regulation by steady-state mechanical cues is well established, how these cues interact with dynamic biochemical signals, such as calcium transients, to control gene-specific transcription remains unclear. We show that intracellular calcium transients act as rapid, tunable inputs that promote YAP nuclear localization and target gene expression, even on soft substrates that normally suppress YAP activity. Low-threshold gene targets are activated broadly, whereas high-threshold targets require stiffer environments, positioning substrate mechanics as a biophysical gate that shapes the magnitude, kinetics, and gene specificity of calcium-mediated YAP responses. These findings provide insights into how cells integrate transient calcium signals with steady-state matrix mechanics to regulate proliferation, differentiation, and tissue behavior","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 387-407"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta BiomaterialiaPub Date : 2026-10-01Epub Date: 2026-09-03DOI: 10.1016/j.actbio.2026.09.006
Yujia Han, Haixiang Zeng, Jing Xu, Hongyan Hao, Hongxia Li, Xiaohui Niu, Yan Li, Xiaoyu Liu, Deyi Zhang, Li Chen, Dongqiang Zhang, Kunjie Wang
{"title":"Zirconium metal-organic framework-based composite drug delivery system for precise drug release and synergistic modulation of the tumor microenvironment in liver cancer therapy","authors":"Yujia Han, Haixiang Zeng, Jing Xu, Hongyan Hao, Hongxia Li, Xiaohui Niu, Yan Li, Xiaoyu Liu, Deyi Zhang, Li Chen, Dongqiang Zhang, Kunjie Wang","doi":"10.1016/j.actbio.2026.09.006","DOIUrl":"10.1016/j.actbio.2026.09.006","url":null,"abstract":"<div><div>Zirconium-based metal-organic framework (MOF-808) materials were selected as drug delivery carriers, with 5-fluorouracil (5-Flu) as the model drug. MOF-808@5-Flu drug-loaded carriers were designed and prepared at different ratios. The drug release behavior of the MOF-808@5-Flu nanocomposite was investigated under different pH conditions (7.4/6.5/5.0). The results showed that when the mass ratio of MOF-808 to 5-Flu was 1:0.25, the material released 55.56% of the drug within 50 h at pH 5.0, compared with 47.85% and 48.00% at pH 7.4 and 6.5, respectively. The drug release behavior was well fitted by the Higuchi model the Higuchi model. Cell and animal experiments demonstrated that MOF-808@5-Flu exhibited good biocompatibility and significantly inhibited the growth of Hepa1–<!--> <!-->6 cells, indicating its potential as a targeted nanocarrier to enhance therapeutic efficacy. Studies indicate that MOF-808@5-Flu induces cancer cell death through the apoptotic pathway. The catalytic activity of Zr<sup>4+</sup> acted synergistically with the pharmacological effects of 5-Flu, generated a large amount of reactive oxygen species (ROS), significantly reducing tumor cell viability. Theoretical calculations indicated that MOF-808@5-Flu exhibits synergistic effects through multiple interactions, including π-π stacking, electrostatic attraction, and hydrophobic interactions. This results further highlights the advantages of MOF-808@5-Flu as a drug delivery platform. In summary, MOF-808@5-Flu shows great potential as a targeted nanocarrier for anticancer drug delivery.</div></div><div><h3>Statement of significance</h3><div>Developed MOF-808@5-Flu nanocarriers with strong potential for targeted anticancer drug delivery. Achieved pH-responsive 5-Flu release, with the highest release rate of 55.56% at pH 5.0 within 50 h. Confirmed that the drug release profile follows the Higuchi model. Demonstrated good biocompatibility and effective inhibition of Hepa1–6 tumor cell growth. Revealed a “carrier-drug” synergistic mechanism driven by Zr<sup>4+</sup> catalysis and multiple intermolecular interactions.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 562-576"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta BiomaterialiaPub Date : 2026-10-01Epub Date: 2025-12-05DOI: 10.1016/j.actbio.2025.12.014
Paula M.C. Torres, Denise Jahn, Nilza Ribeiro, Tiago R. Correia, Miguel Coelho, Tânia S.S. Carvalho, Agnes Ellinghaus, Ana Prates Soares, Carsten Rendenbach, João F. Mano, Katharina Schmidt-Bleek, Susana M. Olhero
{"title":"Enhancing bioactivity of calcium-phosphate cement-based 3D printed scaffolds with human platelet lysates: in vitro and in vivo validation","authors":"Paula M.C. Torres, Denise Jahn, Nilza Ribeiro, Tiago R. Correia, Miguel Coelho, Tânia S.S. Carvalho, Agnes Ellinghaus, Ana Prates Soares, Carsten Rendenbach, João F. Mano, Katharina Schmidt-Bleek, Susana M. Olhero","doi":"10.1016/j.actbio.2025.12.014","DOIUrl":"10.1016/j.actbio.2025.12.014","url":null,"abstract":"<div><div>The reconstruction of large bone defects remains a significant challenge due to the limited regenerative efficacy of engineered biomaterials compared to autologous grafts. Although ceramic substitutes based on calcium phosphates (CaP) have shown promising results for small bone defects, achieving an optimal balance between biological activity and mechanical performance is crucial for the successful repair of larger defects. Enhancing the bioactivity of CaP-based materials through the incorporation of growth factors could be a potential solution. However, the heat treatment required to ensure mechanical performance in ceramic-based products inhibits the incorporation of thermosensitive biomolecules into CaP-based printable formulations, limiting their bioactivity. This study developed apatite cement-based 3D-printed scaffolds with improved bioactivity through the integration of different amounts of human platelet lysates (PL), rich in growth factors, cytokines, and chemokines into the ink formulation. The ink formulations exhibited suitable rheological behaviour for extrusion-based 3D printing, and the scaffolds from all compositions demonstrated good shape fidelity. Remarkably, the delivery of PL from the optimized scaffolds significantly enhanced cell adhesion, proliferation, and function of cells seeded onto the scaffold surfaces compared to the non-loaded scaffolds, as shown in <em>in vitro</em> studies. <em>In vivo</em> studies further revealed that the apatite cement-based scaffolds loaded with 2 wt % of PL are biocompatible and exhibited a good integration into bone, significantly promoting new bone formation within the scaffold pores. This approach presents a promising solution for the repair of large bone defects and establishes these scaffolds as valuable biomaterials in regenerative medicine.</div></div><div><h3>Statement of significance</h3><div>This study presents a promising strategy for advancing bone tissue engineering and regenerating large bone defects. Through synergistic integration of bioactive components and structural optimization, 3D-printable cement-based composite scaffolds combine biological cues with engineered architecture to enhance mechanical and cellular performance. Human platelet lysates improve bioactivity and regenerative potential, while the scaffold’s macroporous design supports bone ingrowth and integration. The material allows for personalization using autologous components, reducing immunogenic risk and improving outcomes. Its architecture, including controlled macroporosity, supports bone integration, as shown by robust <em>in vivo</em> performance with effective tissue incorporation and minimal immune response. This work offers a customizable, biologically potent, and clinically adaptable solution with strong potential for large-scale bone repair and personalized regenerative therapies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"224 ","pages":"Pages 100-119"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}